Diffusion-weighted MR imaging to improve the selection of good and complete responders after chemoradiation therapy in rectal cancer
Projectomschrijving
MRI-scan versus DWI bij endeldarmkanker
Patiënten met lokaal uitgebreide endeldarmkanker worden standaard behandeld met chemo en bestraling gevolgd door een operatie. Soms verdwijnt als gevolg van de chemoradiatie de tumor volledig, in welk geval het achterwege laten van de operatie een aantrekkelijke optie zou zijn, maar alleen wanneer het zeker is dat de tumor inderdaad is verdwenen. Een MRI-scan is onvoldoende betrouwbaar om verdwijnen van tumor met zekerheid vast te stellen. Een alternatief is een PET-scan, hoewel ook PET de respons van de tumor vaak over-/onderschat. Een veelbelovende nieuwe techniek is diffusie-gewogen MRI (DWI). Doel was te onderzoeken of met DWI het verdwijnen van tumor meer betrouwbaar kan worden vastgesteld. Met name het meten van veranderingen in het volume van de tumor op DWI na chemoradiatie is zeer betrouwbaar voor het beoordelen en van het verdwijnen van tumor. Gezien deze veelbelovende resultaten zal de waarde van diffusie-volumetrie in een vervolgstudie verder worden onderzocht voor implementatie.
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Auteur: Beets-Tan RGH, Lambregts DMJ, Maas M, Bipat S, Barbaro B, Caseiro-Alves F, Curvo-Semedo L, Fenlon HM, Gollub MJ, Gourtsoyianni S, Halligan S, Hoeffel C, Kim SH, Laghi A, Maier A, Rafaelsen SR, Stoker J, Taylor SA, Torkzad MR, Blomqvist L.
Magazine: Eur Radiol. 2018 Apr;28(4)
Link: https://doi.org/10.1007/s00330-017-5026-2
Auteur: Curvo-Semedo L, Lambregts DMJ, Maas M, Thywissen T, Mehsen RT, Lammering G, Beets GL, Caseiro-Alves F, Beets-Tan RGH.
Magazine: Radiology 2011 Sep;260(3)
Link: https://doi.org/10.1148/radiol.11102467
Auteur: Lambregts DM, Rao SX, Sassen S, Martens MH, Heijnen LA, Buijsen J, Sosef M, Beets GL, Vliegen RA, Beets-Tan RG.
Magazine: Annals of Surgery 2015 Dec;262(6)
Link: https://doi.org/10.1097/sla.0000000000000909
Auteur: Doenja M. J. Lambregts,1,2 Geerard L. Beets,2 Monique Maas,1,2 Luís Curvo-Semedo,3 Alfons G. H. Kessels,4 Thomas Thywissen,1 and Regina G. H. Beets-Tancorresponding author1
Magazine: European Radiology 2011; 21(12)
Link: https://doi.org/10.1007%2Fs00330-011-2220-5
Auteur: Regina G H Beets-Tan 1, Doenja M J Lambregts, Monique Maas, Shandra Bipat, Brunella Barbaro, Filipe Caseiro-Alves, Luís Curvo-Semedo, Helen M Fenlon, Marc J Gollub, Sofia Gourtsoyianni, Steve Halligan, Christine Hoeffel, Seung Ho Kim, Andrea Laghi, Andrea Maier, Søren R Rafaelsen, Jaap Stoker, Stuart A Taylor, Michael R Torkzad, Lennart Blomqvist
Magazine: Eur Radiol. 2013 Sep;23(9)
Link: https://doi.org/10.1007/s00330-013-2864-4
Auteur: Promovenda: Doenja MJ LambregtsPromotor: Regina GH Beets-TanCo-promotor: Geerard L Beets
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- BACKGROUND: - Standard treatment for locally advanced rectal cancer is a long course of chemoradiation (CRT) followed by surgical resection [1]. After CRT, tumours often show phenomenal downsizing or even disappear. The debate is now whether standard surgery is still necessary for each patient or that less invasive treatments could be an option to reduce morbidity, mortality and costs. Studies have reported good results after local excision for small tumour remnants (ypT1-2) and a ‘wait-and-see' policy for complete responders (ypT0) [2-4]. These treatments are currently considered highly controversial and are only conducted within the scope of clinical trials. This is partly because so far an accurate tumour response evaluation to select the right patients has not been feasible. This is now mainly done with digital examination, rectoscopy and biopsy, which have significant limitations. Clinical adoption of minimally invasive treatments thus strongly depends on whether –and how– we can offer a tool for more accurate patient selection. A recent consensus paper indicated that standard imaging techniques (CT, MRI and ultrasound) are not accurate either and at present the most valuable technique is Fluorodeoxyglucose Positron Emission Tomography (PET) [5, 6]. PET, however, also has limitations: inflammation causes false positive findings (overstaging) and small tumour remnants are missed (understaging) [7-9]. Diffusion-weighted MRI (DWI) is a new technique, for which different studies showed promising results [10-18]. Because the mechanism of DWI differs from that of PET, DWI could potentially be valuable there where PET fails. Additionally, DWI can be added to any standard MRI protocol, is less expensive, and does not require the use of ionising radiation or contrast agents. - OBJECTIVES: - Aim is to evaluate the diagnostic accuracy of DWI for tumour response evaluation in locally advanced rectal cancer and determine its value for the identification of good (ypT1-2) and complete (ypT0) responders who could be selected for minimally invasive treatments instead of standard surgery. Results of DWI will be compared with the imaging tool currently considered most valuable for response evaluation; PET. - STUDY DESIGN: - Multicenter prospective observational cohort study - STUDY POPULATION: - Locally advanced rectal cancer patients undergoing CRT + surgical resection. - INTERVENTION: - DWI is a functional imaging technique based on analysing tissue cellular structure [19]. DWI will be compared to FDG-PET, a technique based on analysing tissue glucose metabolism. PET was chosen as the reference technique to compare with DWI, because so far, PET is the technique that has most widely and successfully been studied for response evaluation in rectal cancer. - OUTCOMES: - 1 The diagnostic performance of DWI (vs. PET) for identification of good and complete responders after CRT. 2 The diagnostic performance of DWI (vs. PET) for early prediction of good and complete responders during CRT. 3 Over- and understaging rates of DWI (vs. PET) 4 Inter/Intra-observer variability in evaluation of DWI data. - SAMPLE SIZE: - The clinically most relevant aim is to decrease the understaging of PET (i.e. improve specificity). A sample size calculation was performed based on previous MUMC results using DWI for complete response prediction (specificity 94% (95% CI 90-97%)) and the assumption that 20% of patients achieve a complete response [20]. The lower limit of the confidence interval (90%) was chosen as the expected specificity. 120 patients are required to obtain a specificity of 91% (95% CI 87%-94%) for identification of a complete response. - DATA ANALYSIS: - The diagnostic accuracy of DWI and PET will be expressed in terms of sensitivity, specificity, positive and negative predictive values, areas under the ROC-curve and 95% confidence intervals. Quadratic kappas and intraclass correlation coefficients will be analysed to evaluate intra- and interobserver reproducibility. The potential impact on patient outcome will be analysed by means of a decision-analytic model. - ECONOMIC EVALUATION: - The main focus is to determine the diagnostic accuracy of DWI (vs. PET). Hence, the estimation of a short-term cost-effectiveness ratio is difficult. We will thus explore the potential cost-effectiveness from a hospital perspective by including the sensitivity and specificity of DWI and PET and their associated costs by performing simple decision analytical modelling. When appropriate, additional data regarding utilities for different treatment strategies and their costs will be based on literature or expert opinion, from which the costs per quality-adjusted life years will be estimated. - TIME SCHEDULE: - Immediate initiation of patient inclusion Year 1: inclusion first 60 patients Year 2: inclusion last 60 patients, data analyses and reporting